Home LiteratureArticle Details
PMID: 21079238 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor.

Reproductive sciences (Thousand Oaks, Calif.) ·Vol. 18 ·No. 1 ·2011-01-00 ·Pages 46-56

Mayor-Lynn K, Toloubeydokhti T, Cruz AC, Chegini N

Abstract

MicroRNAs (miRNAs) have emerged as key regulators of gene expression stability implicated in cell proliferation, apoptosis, and development, whereas their altered expression has been associated with various pathological disorders. The objective of this study was to assess the expression profile of miRNAs and their predicted target genes in placentas from patients with preeclampsia (PC) and preterm (PT) labor as compared to normal term (NT) pregnancies. Using microarray profiling of 820 miRNAs and 18,630 mRNA transcripts, the analysis indicated that 283 of these miRNAs and 9119 mRNAs were expressed in all placentas, of which the relative expression of 20 miRNAs (P < .05 and ≥ 1.5-fold) and 120 mRNAs (P < .05, and 2-fold cutoff) was differentially expressed in PT and PC as compared to NT. The expression of miR-15b, miR-181a, miR-200C, miR-210, miR-296-3p, miR-377, miR-483-5p, and miR-493 and a few of their predicted target genes: matrix metalloproteinases (MMP-1, MMP-9), a disintegrin and metalloproteinase domains (ADAM-17, ADAM-30), tissue inhibitor of metalloproteinase 3 (TIMP-3); suppressor of cytokine signaling 1 (SOCS1); Stanniocalcin (STC2); corticotropin-releasing hormone (CRH), CRH-binding protein (CRHBP); and endothelin-2 (EDN2) were validated in these cohorts using real-time polymerase chain reaction (PCR), some displaying an inverse correlation with the expression of their predicted target genes. Functional analysis indicated that the products of these genes regulate cellular activities considered critical in normal placental functions and those affected by PC and PT labor. In conclusion, the results provide further evidence that placentas affected by PC and PT labor display an altered expression of a number of miRNAs with potential regulatory functions on the expression of specific target genes whose altered expression and function have been associated with these pregnancy complications.

MeSH Terms
Adult Female Gene Expression Profiling Gestational Age Humans MicroRNAs/analysis Obstetric Labor, Premature/metabolism Placenta/chemistry Pre-Eclampsia/metabolism Pregnancy RNA, Messenger/analysis Reverse Transcriptase Polymerase Chain Reaction
Chemicals
MicroRNAs RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mayor-Lynn Kathleen
Department of OB/GYN, University of Florida, Gainesville, FL 32610, USA. gatordoc96@gmail.com
Toloubeydokhti Tannaz
Cruz Amelia C
Chegini Nasser
References (69)
69 references, click to expand
  1. microRNA control of cell-cell signaling during development and disease.
    Cell Cycle. 2008 Aug;7(15):2327-32 PMID: 18677099
  2. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies.
    Am J Obstet Gynecol. 2009 Jun;200(6):661.e1-7 PMID: 19285651
  3. Genetic basis of preterm birth.
    Front Biosci. 2007 Jan 01;12:115-24 PMID: 17127287
  4. MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells.
    Biochem Biophys Res Commun. 2009 Mar 6;380(2):205-10 PMID: 19135980
  5. Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2.
    Endocrinology. 2009 Jan;150(1):452-62 PMID: 18818296
  6. MicroRNA regulation of DNA repair gene expression in hypoxic stress.
    Cancer Res. 2009 Feb 1;69(3):1221-9 PMID: 19141645
  7. MicroRNAs as regulators of epithelial-mesenchymal transition.
    Cell Cycle. 2008 Oct;7(20):3112-8 PMID: 18927505
  8. Prediction and prevention of recurrent preeclampsia.
    Obstet Gynecol. 2008 Aug;112(2 Pt 1):359-72 PMID: 18669736
  9. Genomic and proteomic profiling I: leiomyomas in African Americans and Caucasians.
    Reprod Biol Endocrinol. 2007 Aug 23;5:34 PMID: 17716379
  10. Placental ischemia and cardiovascular dysfunction in preeclampsia and beyond: making the connections.
    Expert Rev Cardiovasc Ther. 2008 Nov;6(10):1367-77 PMID: 19018690
  11. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia.
    Am J Obstet Gynecol. 2007 Mar;196(3):261.e1-6 PMID: 17346547
  12. Neutrophil NETs: a novel contributor to preeclampsia-associated placental hypoxia?
    Semin Immunopathol. 2007 Jun;29(2):163-7 PMID: 17621701
  13. Matrix metalloproteinases and their tissue inhibitors in preterm perinatal complications.
    Reprod Sci. 2007 Oct;14(7):629-45 PMID: 18000225
  14. Decidual cell-expressed tissue factor in human pregnancy and its involvement in hemostasis and preeclampsia-related angiogenesis.
    Ann N Y Acad Sci. 2008 Apr;1127:67-72 PMID: 18443332
  15. Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women.
    Obstet Gynecol. 2007 Nov;110(5):1130-6 PMID: 17978129
  16. Molecular mechanisms of preeclampsia.
    Microvasc Res. 2008 Jan;75(1):1-8 PMID: 17553534
  17. Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review).
    J Protein Chem. 1999 May;18(4):447-65 PMID: 10449042
  18. Genome-wide expression profiling of fetal membranes reveals a deficient expression of proteinase inhibitor 3 in premature rupture of membranes.
    Am J Obstet Gynecol. 2004 Oct;191(4):1331-8 PMID: 15507962
  19. Spontaneous preterm birth, a clinical dilemma: etiologic, pathophysiologic and genetic heterogeneities and racial disparity.
    Acta Obstet Gynecol Scand. 2008;87(6):590-600 PMID: 18568457
  20. Genetic epidemiologic studies of preterm birth: guidelines for research.
    Am J Obstet Gynecol. 2007 Feb;196(2):107-18 PMID: 17306646
  21. The uterine placental bed Renin-Angiotensin system in normal and preeclamptic pregnancy.
    Endocrinology. 2009 Sep;150(9):4316-25 PMID: 19520788
  22. A high-throughput study of gene expression in preterm labor with a subtractive microarray approach.
    Am J Obstet Gynecol. 2001 Sep;185(3):716-24 PMID: 11568803
  23. Preterm birth and inflammation-The role of genetic polymorphisms.
    Eur J Obstet Gynecol Reprod Biol. 2008 Nov;141(1):3-9 PMID: 18783866
  24. MicroRNA targeting specificity in mammals: determinants beyond seed pairing.
    Mol Cell. 2007 Jul 6;27(1):91-105 PMID: 17612493
  25. Detection and characterization of placental microRNAs in maternal plasma.
    Clin Chem. 2008 Mar;54(3):482-90 PMID: 18218722
  26. Angiotensin receptors, autoimmunity, and preeclampsia.
    J Immunol. 2007 Sep 15;179(6):3391-5 PMID: 17785770
  27. The genetic aspects of pre-eclampsia: achievements and limitations.
    Biochem Genet. 2008 Aug;46(7-8):451-79 PMID: 18437552
  28. Biological principles of microRNA-mediated regulation: shared themes amid diversity.
    Nat Rev Genet. 2008 Nov;9(11):831-42 PMID: 18852696
  29. The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts.
    Mol Hum Reprod. 2007 Apr;13(4):273-9 PMID: 17327266
  30. OncomiRs: the discovery and progress of microRNAs in cancers.
    Mol Cancer. 2007 Sep 25;6:60 PMID: 17894887
  31. Differential placental gene expression in preeclampsia.
    Am J Obstet Gynecol. 2008 Nov;199(5):566.e1-11 PMID: 18533121
  32. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3.
    J Biol Chem. 2008 Jun 6;283(23):15878-83 PMID: 18417479
  33. Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse.
    J Endocrinol. 2009 Sep;202(3):337-45 PMID: 19474058
  34. The placenta in preterm birth.
    J Clin Pathol. 2008 Dec;61(12):1261-75 PMID: 19074631
  35. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease.
    Biochem Pharmacol. 2008 Jan 15;75(2):346-59 PMID: 17678629
  36. The role of inflammation and infection in preterm birth.
    Semin Reprod Med. 2007 Jan;25(1):21-39 PMID: 17205421
  37. Principles and effects of microRNA-mediated post-transcriptional gene regulation.
    Oncogene. 2006 Oct 9;25(46):6163-9 PMID: 17028595
  38. Pre-eclampsia: the pivotal role of the placenta in its pathophysiology and markers for early detection.
    Ther Adv Cardiovasc Dis. 2009 Feb;3(1):65-73 PMID: 19124387
  39. Histone deacetylase inhibitor-induced cellular apoptosis involves stanniocalcin-1 activation.
    Exp Cell Res. 2008 Oct 1;314(16):2975-84 PMID: 18652825
  40. Placental corticotrophin-releasing hormone and its receptors in human pregnancy and labour: still a scientific enigma.
    J Neuroendocrinol. 2008 Apr;20(4):432-8 PMID: 18266947
  41. The role of gene-environment interaction in predicting adverse pregnancy outcome.
    Best Pract Res Clin Obstet Gynaecol. 2007 Jun;21(3):491-504 PMID: 17369098
  42. Pre-eclampsia: clinical manifestations and molecular mechanisms.
    Nephron Clin Pract. 2007;106(2):c72-81 PMID: 17570933
  43. MicroRNAs in cancer.
    Annu Rev Pathol. 2009;4:199-227 PMID: 18817506
  44. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
    PLoS One. 2008 Jul 02;3(7):e2557 PMID: 18596939
  45. Pathophysiology of hypertension in response to placental ischemia during pregnancy: a central role for endothelin?
    Gend Med. 2008;5 Suppl A:S133-8 PMID: 18395679
  46. Maternal serum ADAM12s as a potential marker of trisomy 21 prior to 10 weeks of gestation.
    Prenat Diagn. 2008 Mar;28(3):209-11 PMID: 18264948
  47. Hypoxic regulation of miR-210: shrinking targets expand HIF-1's influence.
    Cancer Biol Ther. 2008 Feb;7(2):265-7 PMID: 18347426
  48. Preeclampsia recurrence and prevention.
    Semin Perinatol. 2007 Jun;31(3):135-41 PMID: 17531895
  49. Role of placentally produced inflammatory and regulatory cytokines in pregnancy and the etiology of preeclampsia.
    Semin Immunopathol. 2007 Jun;29(2):151-62 PMID: 17621700
  50. The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression.
    Mol Hum Reprod. 2007 Nov;13(11):797-806 PMID: 17766684
  51. MicroRNAs and chromosomal abnormalities in cancer cells.
    Oncogene. 2006 Oct 9;25(46):6202-10 PMID: 17028600
  52. Mechanisms of microRNA deregulation in human cancer.
    Cell Cycle. 2008 Sep 1;7(17):2643-6 PMID: 18719391
  53. Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis.
    BMB Rep. 2008 Apr 30;41(4):278-86 PMID: 18452647
  54. Expression patterns of microRNAs in the chorioamniotic membranes: a role for microRNAs in human pregnancy and parturition.
    J Pathol. 2009 Jan;217(1):113-21 PMID: 18991333
  55. Inflammatory cytokines in the pathophysiology of hypertension during preeclampsia.
    Curr Hypertens Rep. 2007 Dec;9(6):480-5 PMID: 18367011
  56. Novel biomarkers for predicting preeclampsia.
    Trends Cardiovasc Med. 2008 Jul;18(5):186-94 PMID: 18790389
  57. Molecular evidence of placental hypoxia in preeclampsia.
    J Clin Endocrinol Metab. 2005 Jul;90(7):4299-308 PMID: 15840747
  58. MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy.
    FASEB J. 2008 Dec;22(12):4126-35 PMID: 18716028
  59. Differential placental gene expression in severe preeclampsia.
    Placenta. 2009 May;30(5):424-33 PMID: 19249095
  60. Preeclampsia: increased expression of soluble ADAM 12.
    J Mol Med (Berl). 2005 Nov;83(11):887-96 PMID: 16247621
  61. Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines.
    Hum Reprod. 2007 Jan;22(1):63-74 PMID: 17067994
  62. The impact of microRNAs on protein output.
    Nature. 2008 Sep 4;455(7209):64-71 PMID: 18668037
  63. MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis.
    Exp Hematol. 2007 Apr;35(4):551-64 PMID: 17379065
  64. Expression and regulation of stanniocalcin 1 and 2 in rat uterus during embryo implantation and decidualization.
    Reproduction. 2006 Jun;131(6):1137-49 PMID: 16735553
  65. Epidemiology and causes of preterm birth.
    Lancet. 2008 Jan 5;371(9606):75-84 PMID: 18177778
  66. Altered gene expression of caspase-10, death receptor-3 and IGFBP-3 in preeclamptic placentas.
    Mol Cells. 2006 Oct 31;22(2):168-74 PMID: 17085968
  67. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer.
    Cancer Biol Ther. 2008 Feb;7(2):255-64 PMID: 18059191
  68. The role of decidual natural killer cells in normal placentation and in the pathogenesis of preeclampsia.
    J Obstet Gynaecol Can. 2008 Jun;30(6):467-476 PMID: 18611298
  69. Genetic influences on preterm birth.
    Semin Reprod Med. 2007 Jan;25(1):40-51 PMID: 17205422
Article Info
Journal
Reproductive sciences (Thousand Oaks, Calif.)
Abbr.
Reprod Sci
ISSN
1933-7205
DOI
10.1177/1933719110374115
Email
gatordoc96@gmail.com
Published
2011-01-00
Epub
2010-00-15
Pages
46-56
Language
English
Region
United States
NLM ID
101291249
PMCID
PMC3343068
Subset
IM
Grants
NICHD NIH HHS · R01 HD058664 · United States
NICHD NIH HHS · HD-58664 · United States
External Links
PubMed source DOI: 10.1177/1933719110374115 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2